1. Field of the Invention
The present invention relates to novel kojic acid derivatives, and more particularly it relates to novel 2-mono- or di-hydroxybenzoic acid-substituted kojic acid derivatives having a strong skin whitening activity.
2. Description of Prior Art
Kojic acid, which is obtained from the culture of Aspergillus, has an activity of strongly inhibiting the action of tyrosinase, an enzyme involved in the formation of melanin, which is a major factor in determining the color of human skin. It has been reported that kojic acids inhibit the activity of tyrosinase by forming a chelate with the copper ion in the tyrosinase through the 5-hydroxyl and 4-carbonyl groups. Based on such tyrosinase-inhibiting activity of kojic acid, there have been proposed a lot of cosmetic compositions containing kojic acid as an active ingredient (See JP 56-18569B). Further, JP 54-92632A, JP 56-77272A, JP 60-7961B and JP 60-9722B disclose methods for improving the properties of kojic acid, such as storage stability, compatibility, solubility and the like, and various kojic acid derivatives such as kojic mono- or di-fatty acid esters, having an improved activity of inhibiting tyrosinase. Moreover, JP 3-14508A, JP-4-145096A, JP 4-187618A and JP 5-39298A propose various kojic acid derivatives having a strong tyrosinase-inhibiting activity, such as kojic ethers, glucosylated kojic acids and amino-protected amino acid kojic acids. Furthermore, JP 62-3820B, JP 64-83008A, JP 1-121205A and JP 2-028105A disclose compositions incorporating various additives in order to improve the solubility of kojic acid and to enhance the skin-whitening activity.
The present inventors made extensive researches to develop novel kojic acid derivatives having an improved tyrosinase-inhibiting activity as well as showing a decreased side effect to human skin. As a result thereof, we found that kojic acid derivatives of which the 2-hydroxymethyl group is substituted with mono- or di-hydroxybezoic acid show a superior inhibiting activity on tyrosinase. Particularly, 2-dihydroxybenzoyl kojic acid exhibits an excellent activity of scavenging the radicals, which are known to cause a skin aging, and a decreased side effect to skin.